Since its inception in 1965, the long term goals of this project have been to design, synthesize and evaluate new radiopharmaceuticals as potentials organ or tumor-imaging agents. A specific aim has been to analyze various strategies for accomplishing the site-specific delivery of radiopharmaceuticals to specific tissues. Since these studies have focused on radioiodine as the imaging nuclide, a key factor in achieving the goal has been to select appropriate molecules to serve in the transport of radioiodine to the desired target. Accordingly, the design of the radioiodinated molecules has drawn heavily from current knowledge on the fate and disposition of xenobiotics(e.g. chloroquine-melanin affinity, bretylium-adrenergic neuron) and the synthesis and metabolism of biochemically-important molecules (e.g. cholesterol-adrenal cortex, phospholipid ethers-tumors.) Results with two classes, namely the radioiodinated phospholipid ethers (PLE) and radioiodinated triglyceride analogs, have shown sufficient promise that the current grant period will focus entirely on these agents. For example, several radioiodinated PLE have been shown to accumulate in a variety of tumors including the rat Walker 256 carcinosarcoma, the rabbit Vx2 adenocarcinoma, and human malignant melanoma (HTB63), small cell carcinoma (NCI-69), colon carcinoma(LS-180),and ovarian carcinoma (HTB77)carried in athymic mice. In most instances tumor to blood ratios exceeded 25 and the tumors could be readily imaged in vivo by gamma camera scintigraphy. In a similar manner, certain radioiodinated triglyceride analogs have been shown to be taken up by the liver in concentrations >50% of the administered dose and also to be substrates for both lipoprotein lipase and hepatic lipase such that they are excellent candidates for mapping global and regional hepatic lipid metabolism. Therefore, the goals of this project are (1) to undertake the necessary chemical, pharmacological and toxicological studies with appropriate radioiodinated PLE and triglycerides in order (2) to utilize such data to obtain approval from the Radioactive Drug Research Committee (RDRC) to perform preliminary biodistribution studies in normal volunteers and patients with documented metastatic neoplasms (in the case of PLE) and liver dysfunction (in the case of a triglyceride analog) as a prelude to submission of investigational new drug (I.N.D.) applications for expanded evaluation of clinical efficacy.